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排序方式: 共有1106条查询结果,搜索用时 31 毫秒
1.
Elise Laszlo Gregory De Crescenzo Alfonso Nieto-Argüello Xavier Banquy Davide Brambilla 《Advanced functional materials》2021,31(46):2106061
The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific. 相似文献
2.
Alfonso Martín-Bernab Josep Tarrag-Celada Valrie Cunin Sylvie Michelland Roldn Corts Johann Poignant Cyril Boyault Walid Rachidi Sandrine Bourgoin-Voillard Marta Cascante Michel Seve 《International journal of molecular sciences》2021,22(7)
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献
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S Maruyama T Kurosaki K Sada Y Yamanashi T Yamamoto H Yamamura 《Canadian Metallurgical Quarterly》1996,271(12):6631-6635
Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). We demonstrate here that TPA stimulation increases tyrosine phosphorylation of an 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin. Since tyrosine kinase Syk was activated by TPA stimulation, we examined the possibility that cortactin is a potential substrate of Syk in K562 cells. TPA-induced tyrosine phosphorylation of cortactin was decreased profoundly by overexpression of dominant-negative Syk. Furthermore, cortactin was associated with Syk even before TPA stimulation. Since cortactin was previously referred as an 80/85-kilodalton pp60src substrate, we examined the association between Src and cortactin, whereas its association could not be detected. These data suggest that Syk phosphorylates cortactin in K562 cells upon TPA treatment. 相似文献
5.
Masaaki Miyamoto Hiroyuki Koike Toshio Sada Yasuteru Ijima Junichiro Fukushige Norio Nakamura 《Lipids》1991,26(12):1316-1319
Platelet-activating factor (PAF) is a potent inflammatory mediator which is released by various inflammatory cells and produced
by certain tissues, including the kidney. PAF has been shown to increase glomerular permeability to protein and to decrease
glomerular filtration rate (GFR) by contracting mesangium. On the basis of these observations, it has been suspected that
PAF may play a role as mediator of glomerular damage in glomerular nephritis. To examine this possibility, we studied the
effects of a specific PAF antagonist, R-75,317, on the development of an experimental model of anti-glomerular basement membrane
(anti-GBM) glomerulonephritis. Glomerulonephritis was initiated by injecting rabbit anti-rat GBM serum into rats. Proteinuria
gradually developed after serum injection, plateaued at week 2, and remained at the high level of week 2 throughout the experimental
period (6 wk). Chronic treatment with R-75,317 (10 mg/kg/day i.p.) tended to delay the onset of proteinuria and significantly
accelerated the recovery phase. Creatinine clearance (Ccr) fell to 40% at week 3. R-75,317 treatment completely prevented
this decline of Ccr. Histological changes in this model (glomerular hypertrophy, proliferation of mesangial matrix and interstitial
fibrosis) were also ameliorated by the R-75,317 treatment. The results suggest that PAF may play a role in the development
of glomerulonephritis and that PAF antagonists could be used in the treatment of human renal disease.
Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl
Ether Lipids, May 1989. 相似文献
6.
Sebastián Bruque-Cámara Alfonso Vargas-Sánchez M. Jesús Hernández-Ortiz 《欧洲信息系统杂志》2004,13(2):133-146
The aim of this paper is to propose new organizational factors that might explain the differences in the extent and the speed of IT adoption. With this in mind, we carried out an analysis of 16 cases in the pharmaceutical distribution sector in Spain. The results indicate that there are certain intangible assets that favour the introduction and development of IT. Among these are a frank and fluid communication between departments and members of the organization, low levels of conflict, the explicit support of top management towards IT adoption and learning and creative skills of IT-staff. In addition to these factors, we found others that we propose as catalysts of IT adoption. Among these we might mention the special relationship between the member-clients and the company in the case of cooperative firms. 相似文献
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Gradient-corrected density functional theory was used to investigate the adsorption of H2S on Pd(1 1 1) surface. Molecular adsorption was found to be stable with H2S binding preferentially at top sites. In addition, the adsorption of other S moieties (SH and S) was investigated. SH and S were found to be preferentially bind at the bridge and fcc sites, respectively. The reaction pathways and energy profiles for H2S decomposition giving rise to adsorbed S and H were determined. Both H2S(ad) → SH(ad) + H(ad) and SH(ad) → S(ad) + H(ad) reactions were found to have low barriers and high exothermicities. This reveals that the decomposition of H2S on Pd(1 1 1) surface is a facile process. 相似文献
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10.
Costa Albert; Kovacic Damir; Fedorenko Evelina; Caramazza Alfonso 《Canadian Metallurgical Quarterly》2003,29(6):1270
The authors report 3 picture-word interference experiments in which they explore some properties of the agreement process in speech production. In Experiment 1, Croatian speakers were asked to produce utterances in which the noun's gender value had an impact on the selection of gender-marked freestanding morphemes (pronouns) while ignoring the presentation of same- or different-gender distractor words. In Experiments 2 and 3, Croatian speakers were asked to name the same pictures using noun phrases in which the noun's gender value surfaced as an inflectional suffix. Different-gender distractors interfered more than same-gender distractors (the gender congruency effect) in Experiment 1, but not in Experiments 2 and 3. These contrasting results show that the cause of the gender congruency effect is not at the level where lexical-grammatical information is selected but at the level of selection of freestanding morphemes. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献